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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5986_Библиотеки_им_академика_М_И_Перельмана.pdf
67
Volumetric Analysis
N
N
N
CH
2
SO
3
Na
H
3
C CH
3
CH
3
.H
2
O
O
Molecular weight: 334 (without water molecule)
Indicator: Iodine itself
IP limit: It contains not less than 99.0% w/w and not more than 100.5%
C
13
H
17
O
4
N
3
NaS, calculated with reference to the dried substance.
Procedure
Weigh accurately a quantity of the powder equivalent to about 0.4 g of
metamizole and dissolve it in a mixture of 40 mL of ethanol (95%) and 10 mL
of 0.01 M hydrochloric acid and titrate with 0.05 M iodine until yellow colour
stable for 30 s is produced.
or
Pipette out 10 mL of metamizole alcoholic solution. To it add 3 mL of 0.01 M
hydrochloric acid and titrate the solution with previously standardized iodine
solution till a yellow colour that remains stable for 30 s.
Reaction involved
Metamizole (keto form)
H
N
N
N
CH
2
SO
3
Na
H
3
C CH
3
CH
3
.H
2
O
O
Metamizole (enol form)
N
N
N
CH
2
SO
3
Na
H
3
C CH
3
CH
3
.H
2
O
HO
N
N
N
CH
2
SO
3
H
H
3
C CH
3
CH
3
.H
2
O
OH
Metamizole (irreversible form)
THEORY Metamizole sodium, also known as Dipyrone, Analgin, Novalgin and
Melubrin, is a nonsteroidal anti-inflammatory drug. Iodine oxidizes the keto form
of metamizole to enol form. This is a reversible reaction. To prevent the backward
reaction hydrochloric acid is added which convert metamizole into irreversible
form.
68
Practical Pharmaceutical Analytical Chemistry
Equivalent factor
I
2
{ 2I C
13
H
17
O
4
N
3
NaS { 2e
2 u 1000 mL of 1 N I
2
{ {(13 u 12) (17 u 1) (4 u 16) (3 u 14) (1 u
23) (1 u 32)}g of metamizole
2 u 1000 mL of 1 N iodine
{ {156 17 64 42 23 32}g of metamizole
1000 mL of 1 N iodine
{ (334/2) g of metamizole 167 g of metamizole
1 mL of 1 N iodine { (167/1000) g of metamizole 0.167 g of metamizole
Calculation
1 mL of 1 N iodine { 0.167 g of metamizole
a mL of 1 N iodine { (0.167 u a) g of metamizole
a mL of yN iodine { (0.167 u a u y) g of metamizole
Since 10 mL of metamizole solution contains (0.167 u a u y) g of metamizole
1 mL will contain {(0.167 u a u y)/10}g of metamizole
100 mL will contain {(0.167 u a u y u 100)/10}g of metamizole
So
g mL of Metamizole
Equivalent factor Burette reading
Normal
/100 =
u
u
iity I
2
100
10
()
u
Pharmaceutical use
1. It is used as analgesic.
2. It is used as antipyretic.
Category: NSAID
Result The given metamizole solution was found to contain _______
g/100 mL of metamizole.
Experiment 15 To find out g/100 mL of paracetamol (acetaminophen) in
the given sample.
IP followed: 1996
Principle: Redox titration
Molecular formula: C
8
H
9
O
2
N
NHCOCH
3
OH
69
Volumetric Analysis
Molecular weight
144
Indicator: Ferroin
IP limit: It contains not less than 99.0% and not more than 101.0% of
C
8
H
9
O
2
N, calculated with reference to the dried substance.
Procedure
Weigh accurately 0.5 g of paracetamol and dissolve it in a mixture of 10 mL of
water and 50 mL of 1 M sulphuric acid. Boil the reaction mixture for 1 h, cool
and dilute it to 100 mL with water. Pipette out 20 mL of the solution and to
it further add 40 mL of water, 40 g of water in the form of ice, 15 mL of 2 M
hydrochloric acid and titrate it with 0.1 M cerric ammonium sulphate using
ferroin solution as an indicator till a yellow colour that remains stable for 30 s is
produced. Similarly also perform a blank titration.
Reaction involved
Benzoquinone
H
p-AminophenolAcetaminophen (paracetamol)
NHCOCH
3
OH
NH
2
OH
O
O
4Ce(IV)
2[O]
H
2
O
NH
3
+
+
Water Ammonia
THEORY Sulphuric acid causes the hydrolysis of acetaminophen into p-ami-
nophenol by deacetylation reaction. Cerric ammonium sulphate causes the
oxidation of p–aminophenol into benzoquinone. The difference in two titra-
tion (actual and blank) gives the actual amount of cerric ammonium sulphate
required for oxidation.
Equivalent factor
C
8
H
9
O
2
N { 2[O]
2 u 1000 mL of 1 M cerric ammonium sulphate { {(8 u 12) (9 u 1) (2 u
16) (1 u 14)}g of paracetamol
2 u 1000 mL of 1 M cerric ammonium sulphate { {96 9 32 14}g of
paracetamol
2 u 1000 mL of 1 M cerric ammonium sulphate { 151 g of paracetamol
1000 mL of 1 M cerric ammonium sulphate { (151/2) g of paracetamol
75.5 g of paracetamol
1 mL of 1 M cerric ammonium sulphate { (75.5/1000) g of paracetamol
0.0755 g of paracetamol
70
Practical Pharmaceutical Analytical Chemistry
Calculation
1 mL of 1 M cerric ammonium sulphate { 0.0755 g of paracetamol
a mL of 1 M cerric ammonium sulphate { (0.0755 u a) g of paracetamol
a mL of yM cerric ammonium sulphate { (0.0755 u a u y) g of paracetamol
Since 10 mL of paracetamol solution contains (0.0755 u a u y) g of paracetamol
1 mL will contain {(0.755 u a u y)/10}g of paracetamol
100 mL will contain {(0.0755 u a u y u 100)/10}g of paracetamol
So
g mL of Paracetmol
Equivalent factor Burette reading
Molari
/100 =
u
u
tty cerric ammonium sulphate
()
u 100
10
Pharmaceutical use
1. It is used as an analgesic and pain killer.
2. It is used as an antipyretic.
Category: Analgesic; Antipyretic
Result The given paracetamol solution was found to contain _______
g/100 mL of paracetamol.
2.3 Precipitation Titration
Precipitation means formation of precipitate or insoluble complex and
precipitation titration is that titration which involves the formation of precipitate.
The most important precipitating reagent is silver nitrate. The reaction which
involves the interaction of silver nitrate with halides present in the sample is also
known as argentometric titration. Similarly some reactions also involve analysis
of compound of silver and mercury by direct titration with standard ammonium
thiocyanate solution. The formation of precipitate is quantitative in nature. The
end point in these can be detected by using the following:
1. Cessation of precipitate
2. Using potentiometric or amperometric methods
3. Indicators:
a. Indicator which forms a coloured precipitate like potassium chromate
which forms an orange precipitate of silver chromate after reaction
with silver nitrate.
b. Indicators which form coloured solution like ferric ammonium
sulphate.
71
Volumetric Analysis
c. Adsorption indicator, a dye like rhodamine is used, which gets adsorbed
on the surface of precipitate and gives a different colour to detect the
end point.
The limited application of precipitation titration is due to the following reasons:
1. Lack of suitable indicators
2. In some cases particularly in the titration of dilute solutions, the rate of
reaction is too slow for a convenient titration.
3. Composition of the precipitate sometimes is not fixed due to the co–
precipitation so that the stoichiometry of the reaction is not definite caus-
ing error.
2.3.1 Classification
Precipitation method can be classified into two main categories:
1. Mohr’s method
2. Volhard’s method
Mohr’s method (1856)
This is also known as the direct method. In this method halides of sodium or
potassium are estimated by titration with silver nitrate solution. When all the
halides are precipitated as silver halides, the silver nitrate reacts with the indicator,
potassium chromate solution to give a red precipitate of silver chromate. This
type of titration is limited to solution with pH value 610. In acid solution,
potassium chromate cannot be used as an indicator, because chromate ion is the
conjugate base of the weak chromic acid. Therefore, when the pH is lower than
6, chromate ion is protonated and the chromic acid is predominately formed in
the solution. Similarly, if the pH is more than 10, brownish silver hydroxide is
formed which interferes with the end point colour. Hence, alkaline solution may
be neutralized with dilute nitric acid and solutions which are too acidic may be
neutralized by sodium carbonate or calcium carbonate or buffer acetate.
Disadvantages of Mohr’s Method
s Ions such as phosphates, arsenates, sulphides are also precipitated.
s The end point is less sensitive when titration involves dilute solution.
s Adsorbed ions on precipitate of sample become trapped and leads to
wrong result.
s Vigorous shaking is required near the end point to free the trapped
ion.
s In the acid solution, potassium chromate cannot be used because of
the solubility of silver chromate in acids.
s Iodides and bromides cannot be titrated because their precipitates are
brown in colour and so they would be interfering with the end point.
72
Practical Pharmaceutical Analytical Chemistry
Volhard’s Method (1874)
This is the most common method used to determine the halide/halogen content
in acid solution. In this method, halides are completely precipitated as silver halide
by excess of silver nitrate solution and determining the amount of unreacted
silver nitrate solution by residual titration with standard ammonium thiocyanate
solution using ferric alum as an indicator. The precipitate of silver chloride is
separated by filtration or coated by some organic solvents like nitrobenzene or
dibutyl phthalate.
Modification of Volhard’s Method
s In determining the chlorinated compounds in benzoic acid, sodium
benzoate and benzyl alcohol, silver chloride is precipitated in a warm
solution in the presence of amyl alcohol in order to coagulate the
precipitate of silver chloride at wateramyl alcohol interface. This
prevents the interaction of silver chloride with titrant.
s In determining the chlorinated compounds in vinyl ether,
chlorbutanol, dicophane in the assay of ammonium chloride modified
Volhard’s method is applied. Silver chloride is precipitated in a solution
containing a small amount of nitrobenzene. This coats the precipitate
and prevents the interaction between silver chloride and the titrant.
Sources of Errors in Volhard’s Method
In titration of silver with thiocyanate, some silver is adsorbed by precipitate thus
leading to a premature end point. This difficulty may be overcome by simply
shaking mixture vigorously which helps to remove the unreacted silver from the
precipitate.
In addition, the other two more methods are:
Fajan’s Method (1924)
This method involves the adsorption indicator for the detection of end point.
It is based on the concept that at the end point indicator gets adsorbed by the
precipitate to give different colour.
Gaylussac’s Method
This is the method which indicates the end point by appearance of turbidity
instead of using indicators. It is also known as turbidity method.
Example:
Titration of sodium bromide with silver nitrate
AgNO NaBr AgBr
Silver nitrate
Sodium bromide
Silver bromide
3
+⎯→⎯⎯⎯ ++ NaNO
Sodium nitrate
3
73
Volumetric Analysis
In this titration, precipitation of silver bromide occurs only as long as an excess
of bromide ion is present in the solution. One can detect the end point by taking
a small portion of the titrated solution at the end of titration and adding a single
drop of the silver nitrate solution diluted to tenfold (see Tables 2.3 and 2.4).
Table 2.3 Comparative evaluation of Mohr’s, Volhard’s, Fajan’s and Gaylussac’s method
Parameters Mohr’s Volhard’s Fajan’s Gaylussac’s
1. Type Direct Indirect Direct Direct
2. Indicator used Potassium
chromate
Ferric ammonium
sulphate
Adsorption indicator
like fluorscein
No indicator
3. Assay of Chlorides
and
fluorides
Halides, i.e. bromides
and iodides can also
be evaluated
Chlorides, bromides,
iodides and fluorides
All halides
4. Colour change
or end point
Brick red
precipitate
Brick red solution Pink colour Turbidity
5. pH nature Neutral or
pH 6
10
Acidic
Acidic or alkaline Acidic or
alkaline
6. Process
involved
Solubility
product
Solubility product Physisorption
(surface adsorption)
Solubility
product
Table 2.4 Common precipitation titrations indicators used in Mohr’s, Volhard’s and Fajan’s method
Indicators Nature of
titration
Use or application Experimental
conditions
End point
1. Potassium
chromate
Mohr’s Chlorides and fluorides Neutral Brick red
precipitate
2. Ferric
ammonium
sulphate
Volhard’s Halides, i.e. bromides
and iodides can also be
evaluated
Acidic Brick red
solution
3. Fluorescein Fajan’s Halides, i.e. bromides
and iodides can also be
evaluated
Neutral or weakly
basic solution
Pink colour
4. Tetrazine Fajan’s Silver with iodide or
thiocyanate—excess silver
on back titration, i.e.
iodide
Acidic or alkaline
(Back titration)
Green
5. Dichloro-
fluorescein
Fajan’s Chloride, bromides with
silver
pH 4.47
Red
74
Practical Pharmaceutical Analytical Chemistry
2.3.2 Indicators
Ferric Ammonium Sulphate
It is prepared by dissolving 8 g of reagent ferric ammonium sulphate in sufficient
distilled water and make the volume to 100 mL with distilled water. This is used
in both direct and residual titrations of silver and mercury salts with standard
ammonium thiocyanate solution. The thiocyanate reacts with the silver or
mercury present to form a white precipitate of silver or mercury thiocyanate,
but as soon as all of the silver or mercury has been precipitated the thiocyanate
reacts with ferric ammonium sulphate to form red ferric sulphocyanate. The
appearance of red colour indicates the end point of the reaction.
Fe NH SO NH SCN
Ferric ammonium sulphate
Ammonium thiocya
44
2
4
3
()()
+
nnate
Ferric thiocyanate
Brick red colour
Fe SCN NH⎯→⎯⎯⎯
()
+
()
()
3
24
22
4
SO
Ammonium sulphate
Potassium Chromate
It is prepared by dissolving 10 g of potassium chromate in 100 mL of distilled
water. It is used in the direct method. At the end point potassium chromate reacts
with silver nitrate to give red colour precipitate of silver chromate.
Potassium chromate must be present at a concentration of at least 0.0058 M if
precipitation is to occur at the end point (calculation is based on the solubility
product determined at 25qC). High concentrations of potassium chromate tend
to obscure the end point which causes the addition of small excess of silver
nitrate before the eye can detect, the change which can be corrected by a blank
determination.
AgNO K CrO Ag CrO
Silver nitrate
Potassium chromate
Silv
324 24
+⎯→⎯⎯⎯
eer chromate
Brick red colour
Potassium nitrate
KNO
()
+ 2
3
Adsorption Indicator
Besides potassium chromate and ferric ammonium sulphate, adsorption indicators
like fluorescein and eosin are also used in the estimation of halides.
The action of these indicators is due to the fact that at the equivalence point
the indicator is adsorbed by the precipitate and during the process of adsorption
a change occurs in the indicator which leads to a substance of different colour.
They have therefore termed it as adsorption indicators. The substances employed
are either acid dyes such as those of the fluorescein series like fluorescein and
eosin which are utilized as the sodium salts or basic dyes such as those of the
rhodamine series like rhodamine 6G which are used as the halogen salts.
The theory of action of these indicators is based upon the properties of colloids.
When a chloride solution is titrated with a solution of silver nitrate, the precipitated
75
Volumetric Analysis
silver chloride adsorbs chloride ions. This may be termed as the primary adsorbed
layer. By a process known as secondary adsorption, oppositely charged ions present
in solution are held around it. As soon as the equivalence point is reached, silver
ions are present in excess and these now become primarily adsorbed; nitrate ions
will be held by secondary adsorption. If flourescein is also present in the solution,
the negative flourescein ion which is much more strongly adsorbed than is the
nitrate ion, is immediately adsorbed and will reveal its presence on the precipitate
by the formation of a pink complex of silver and a modified fluorescein ion on the
surface. It is important to notice that the colour change takes place at the surface of
the precipitate. The change is reversible upon the addition of chloride.
2.3.3 Condition for Good Precipitation Titration
1. The rate of reaction between the precipitant and the substance to be
precipitated must be fast.
2. The reaction between the analyte and the reagent should proceed accord-
ing to a definite stoichiometric relationship.
3. There should not be any coprecipitation.
4. A suitable indicator should be available to indicate the end point.
2.3.4 Equivalent Weight in Precipitation Titration
Equivalent weight can be calculated by using the formula:
Equivalent weight of ecipi t
Molecular weight
Valency of prec
Pr tan
iipitating ion
For example, sodium chloride is used as precipitant for precipitating silver
chloride from silver nitrate solution. Here the precipitating ion is Cl
1
ion the
valency of which is one, so
Equivalent weight of Sodium chloride
Molecular weight
1
The equivalent weight of the substance containing the ion which is precipitated
is given by
Equivalent weight of
Subs ce to be precipitated
Molecular weigh
tan
tt
Valency of the ion that is precipitated
For example, sodium chloride is added to silver nitrate solution, Ag
ion is
precipitated as silver chloride, hence
Equivalent weight of Silver nitrate
Molecular weight
1
76
Practical Pharmaceutical Analytical Chemistry
Experiment 1 To prepare and standardize 0.1 M silver nitrate.
Primary standard Sodium chloride (NaCl)
Indicator: Potassium chromate (K
2
CrO
4
)
Method
s Preparation: Weigh accurately 169.9X g of silver nitrate and dissolve it
in water. Finally, adjust the volume to 1 L to give XM or XN solution.
s Standardization: Dry some AR grade at 300qC for 2 h (to remove
moisture), cool in dessicator and use to prepare an accurate 0.1 M
solution of sodium chloride. Pipette 25 mL of the 0.1 M sodium
chloride solution in a conical flask, add potassium chromate solution
(5% w/w; 1 mL) and titrate it with the silver nitrate solution. Continue
to titrate until reddish brown colour is observed.
End point: Appearance of reddish brown precipitate.
Reaction involved
AgNO NaCl AgCl
Silver nitrate
Sodium chloride
Silver chlori
3
+⎯→⎯⎯⎯
dde
White ppt
Sodium nitrate
Silver nitrate
NaNO
AgNO K CrO
.
()
+
+
3
324
PPotassium chromate
Silver chromate
Brick red colour
Ag CrO⎯→⎯⎯⎯
24
(()
+ 2
3
KNO
Potassium nitrate
Calculation
M
1
u V
1
M
2
u V
2
where M
1
is the molarity of given silver nitrate solution, V
1
is the volume of
silver nitrate, i.e. burette reading, M
2
is the molarity of given sodium chloride
solution and V
2
is the volume of sodium chloride taken.
Result The prepared silver nitrate solution was found to be
Experiment 2 To prepare and standardize 0.1 M ammonium thiocyanate.
Primary standard Previously standardized silver nitrate (AgNO
3
)
Indicator: Ferric ammonium sulphate or ferric alum [Fe(NH
4
)(SO
4
)
2
]
Method
s Preparation: Weigh accurately 76.12X g of ammonium thiocyanate and
dissolve it in water. Finally, adjust the volume to 1 L to give XM or
XN solution.